Encephalopathy pathogenesis

Rifaximin has been shown to possess good antibacterial activity against a variety of anaerobic bacteria (table 3) [24, 27, 28], Anaerobes have been shown to be capable of producing ammonia (especially Clostridia), which has been incriminated in the pathogenesis of hepatic encephalopathy [29], The authors suggested that since rifaximin is a nonabsorbable and effective antibiotic against anaerobic flora, it would be an ideal treatment for patients with compromised hepatic function. Eubacterium is inhibited by rifaximin with an MIC90 < 2 pg/ml [27]. 

BassNEI. 1968. Pathogenesis of myelin lesions in experimental cyanide encephalopathy. Neurology 18 167-177. 

Pepin J, Milord F (1991) African trypanosomiasis and drug-induced encephalopathy risk factors and pathogenesis. Trans R Soc Trop Med Hyg 85 222-224... 

Langlais PJ (1995) Pathogenesis of diencephalic lesions in an experimental model of Wernicke s encephalopathy. Metabolic Brain Diseases 10, 31-44. 

Okeda, R., Funata, N., Takano, T., Manabe, M. (1981). The pathogenesis of carbon monoxide encephalopathy in the acute... 

Owing to the multitude of factors interfering with the ammonia concentration as well as to the multifactorial pathogenesis of hepatic encephalopathy (HE), it is understandable that there is no correlation between the levels of ammonia and the prevailing HE stage. Nevertheless, a hyperammonia syndrome is generally presumed if concentrations in the venous or arterial plasma reach 135-170 4g/dl. A value of > 150 gg/dl can be attributed to coma stage I. Here, the arterial ammonia level correlates better with HE than do the values found in venous blood, (s. pp 56, 266)... 

In the case of cerebral dysfunction, it is possible for these disorders to be reflected individually in differing states of intensity and in a variety of combinations. This results in a very varied pathophysiological and clinical picture of encephalopathy. Such a collective term for restrictions in the function of the brain does not, however, yield any statement as to their origins or pathogenesis. Encephalopathy can be triggered by some 50-60 disorders and aetiological factors - including liver diseases. (see chapter 15)... 

Basile, A.S., Jones, E.A., Skolnick, P. The pathogenesis and treatment of hepatic encephalopathy evidence for the involvement of benzodiazepine receptor ligands. Pharmacol. Rev. 1991 43 27-71... 

Goldstein, G.W. The role of brain capillaries in the pathogenesis of hepatic encephalopathy. Hepatology 1984 4 565-567... 

Jalan, R., Seery, J.P., Taylor-Roblnson, S.D. Review article pathogenesis and treatment of chronic hepatic encephalopathy Aliment. Pharmacol. Ther. 1996 10 681-697... 

Levy, L.J., Losowsky, M.S. Plasma gamma aminobutyric acid concentrations provide evidence of different mechanisms in the pathogenesis of hepatic encephalopathy in acute and chronic hver disease. Hepato-Gastroenterol. 1989 36 494-498... 

Odeh, M. Endotoxin and tumor necrosis factor- in the pathogenesis of hepatic encephalopathy. J. Clin. Gastroenterol. 1994 19 146-153... 

Venturini, L, Corsi, L., Avallone, R., Farina, F., Bedogni, G., Baraldi, C., Baraldi, M., Zeneroli, M.L. Ammonia and endogenous benzodia-zepine-like compounds in the pathogenesis of hepatic encephalopathy. Scand. J. Gastroenterol. 2001 36 423-425... 

Walker, C.O., Schenker, S. Pathogenesis of hepatic encephalopathy with special reference to the role of ammonia. Amer. J. Clin. Nutr. 1970 23 619-632... 

However, the emergence of variant Creutzfeldt-Jakob disease (vCJD) in the UK and France has raised concern about a new theoretical risk of infection in patients treated with blood and blood products (198). Animal experiments in which blood from sheep infected with bovine spongiform encephalopathy and natural scrapie-infected sheep into scrapie-free recipient animals have suggested disease transmission by the blood transfusion route in 2 of 24 sheep with bovine spongiform encephalopathy and in 4 of 21 sheep with scrapie (199). Many European countries have incorporated leukodepletion of all blood products, as leukocytes are believed to play a key role in the pathogenesis of variant Creutzfeldt-Jakob disease (198). In some countries, people who have lived in the UK for a period longer than 6 months between 1980 and 1996 are excluded from blood donation (13). Furthermore, it has been shown that various steps used in the manufacture of plasma-derived products also contribute to reduced infectivity by bovine spongiform encephalopathy (198). 

Venturini I, Corsi L, AvaUone R, Farina F, Bedogni G, Baraldi C, et al. Ammonia and endogenous benzodi-azepine-like compounds in the pathogenesis of hepatic encephalopathy. Scand J Gastroenterol 2001 36 423-5. 

Secondary hyperaldosteronism plays a major role in the pathogenesis of edema in patients with cirrhosis. Therefore these patients should initially be treated with spironolactone in the absence of impaired GFR and hyperkalemia. Thiazides may then be added for patients with a creatinine clearance >50 mL/min. For those patients who remain diuretic resistant, a loop diuretic may replace the thiazide. Patients with impaired GFR (creatinine clearance of <30 mL/min) generally will require a loop diuretic, with addition of a thiazide in those who do not achieve adequate diuresis. Care should be taken to avoid hypokalemia, which may precipitate hepatic encephalopathy by increasing ammoniagenesis (Fig. 49-8). ... 

Layrargues GP, et al. Role of manganese in the pathogenesis of portal-systemic encephalopathy. Metab Brain Dis 1998 13 311-317. 

Der Trab ist auch eine Krankheit der Schaafe, und ist ansteckend. Sie schleppen sich lange, verzehren sich nach und nach, und zuletzt miissen sie sterben. These sentences are taken from an article published in 1759 [1] and describe two hallmarks of prion diseases or transmissible spongiform encephalopathies (TSEs, summarized in Table 1) The formation and transmission of an infectious particle and the invariably fatal course of these diseases. More than 200 years later a landmark discovery paved the way to study the pathogenesis of prion diseases at a molecular level. Prusiner and colleagues reported the identification of a protease-resistant protein in brain extracts, which co-purified with the infectious scrapie agent [18]. After the N-terminal amino acid sequence of the proteinase K (PK)-resistant core of the prion protein (PrP 27-30) was published in 1984 [19], two... 

A study by Rao et al." measured the levels of amino acids using in vivo cerebral microdialysis in the frontal cortex of portacaval-shunted rats administered ammonium acetate to precipitate severe portal-systemic encephalopathy. In comparison to sham-operated control rats, tryptophan levels increased by 63% along with those of other amino acids. However, the experimental animals did not have a significant increase in extracellular fluid concentration of tryptophan, suggesting that increased spontaneous release of tryptophan in cerebral cortex is not implicated in the pathogenesis of hepatic coma. 

---